e54c15627b3d291be2391384ec331585 pmc_34768418.pdf 6b7f6ee7e1227153e153baa34e06774d902e0f93 pmc_34768418.pdf 788ae0c90fa75d9c5d0e62b600bef1b3be2c5d3b5dd14613c01b7c91563d9633 pmc_34768418.pdf Title: Voluntary Modulation of Evoked Responses Generated by Epidural and Transcutaneous Spinal Stimulation in Humans with Spinal Cord Injury Subject: Transcutaneous (TSS) and epidural spinal stimulation (ESS) are electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot-phase clinical trials using ESS and TSS have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS pulses with spared descending connections across the site of SCI have yet to be characterized. Therefore, we examined the effects of delivering TSS or ESS pulses to the lumbosacral spinal cord in nine individuals with chronic SCI. During low-frequency stimulation, participants were instructed to relax or attempt maximum voluntary contraction to perform full leg flexion while supine. We observed similar lower-extremity neuromusculature activation during TSS and ESS when performed in the same participants while instructed to relax. Interestingly, when participants were instructed to attempt lower-extremity muscle contractions, both TSS- and ESS-evoked motor responses were significantly inhibited across all muscles. Participants with clinically complete SCI tested with ESS and participants with clinically incomplete SCI tested with TSS demonstrated greater ability to modulate evoked responses than participants with motor complete SCI tested with TSS, although this was not statistically significant due to a low number of subjects in each subgroup. These results suggest that descending commands combined with spinal stimulation may increase activity of inhibitory interneuronal circuitry within spinal sensorimotor networks in individuals with SCI, which may be relevant in the context of regaining functional motor outcomes. Keywords: spinal cord injury; electrically evoked spinal motor potentials; spinal cord stimulation; neuromodulation Author: Jonathan S. Calvert, Megan L. Gill, Margaux B. Linde, Daniel D. Veith, Andrew R. Thoreson, Cesar Lopez, Kendall H. Lee, Yury P. Gerasimenko, Victor R. Edgerton, Igor A. Lavrov, Kristin D. Zhao, Peter J. Grahn and Dimitry G. Sayenko Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Oct 27 04:00:24 2021 CEST ModDate: Wed Oct 27 10:24:00 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1785963 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- PSUYZB+VnURWPalladioL Type 1 Custom yes yes no 10 0 QBQJIQ+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 EOLSVW+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 UUGUVK+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 32 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 35 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 57 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 61 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 65 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 77 0 JYUNWZ+CMSY10 Type 1 Builtin yes yes no 81 0 APNIKC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 88 0 APNILD+PalatinoLinotype TrueType WinAnsi yes yes no 91 0 APNILF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 94 0 APNIKC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 113 0 APNILD+PalatinoLinotype TrueType WinAnsi yes yes no 116 0 APNILF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 119 0 APNIKC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 127 0 APNILD+PalatinoLinotype TrueType WinAnsi yes yes no 130 0 APNILF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 133 0 APNIKC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 144 0 APNILC+PalatinoLinotype CID TrueType Identity-H yes yes yes 147 0 APNILD+PalatinoLinotype TrueType WinAnsi yes yes no 153 0 APNILF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 156 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-22 02:36:38 CET RepresentationInformation: pmc_34768418.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-01-11 05:14:51 CET Size: 1785963 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 390 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Description of Participants Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Data Acquisition Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Stimulation Procedures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Data Processing and Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Epidural and Transcutaneous Spinal Stimulation in the Same Participants Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Effect of Voluntary Effort on Spinally Evoked Responses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Effect of Stimulation Modality and Injury Severity on Voluntary Modulation of Evoked Responses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Info: Title: Voluntary Modulation of Evoked Responses Generated by Epidural and Transcutaneous Spinal Stimulation in Humans with Spinal Cord Injury Author: Jonathan S. Calvert, Megan L. Gill, Margaux B. Linde, Daniel D. Veith, Andrew R. Thoreson, Cesar Lopez, Kendall H. Lee, Yury P. Gerasimenko, Victor R. Edgerton, Igor A. Lavrov, Kristin D. Zhao, Peter J. Grahn and Dimitry G. Sayenko Subject: Transcutaneous (TSS) and epidural spinal stimulation (ESS) are electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot-phase clinical trials using ESS and TSS have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS pulses with spared descending connections across the site of SCI have yet to be characterized. Therefore, we examined the effects of delivering TSS or ESS pulses to the lumbosacral spinal cord in nine individuals with chronic SCI. During low-frequency stimulation, participants were instructed to relax or attempt maximum voluntary contraction to perform full leg flexion while supine. We observed similar lower-extremity neuromusculature activation during TSS and ESS when performed in the same participants while instructed to relax. Interestingly, when participants were instructed to attempt lower-extremity muscle contractions, both TSS- and ESS-evoked motor responses were significantly inhibited across all muscles. Participants with clinically complete SCI tested with ESS and participants with clinically incomplete SCI tested with TSS demonstrated greater ability to modulate evoked responses than participants with motor complete SCI tested with TSS, although this was not statistically significant due to a low number of subjects in each subgroup. These results suggest that descending commands combined with spinal stimulation may increase activity of inhibitory interneuronal circuitry within spinal sensorimotor networks in individuals with SCI, which may be relevant in the context of regaining functional motor outcomes. 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